Publications by authors named "Hongjuan Li"

96 Publications

Assembly of multifunction dyes and heat shock protein 90 inhibitor coupled to bovine serum albumin in nanoparticles for multimodal photodynamic/photothermal/chemo-therapy.

J Colloid Interface Sci 2021 May 27;590:290-300. Epub 2021 Jan 27.

Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Shaanxi 712100, PR China. Electronic address:

The proangiogenic protein, survivin, is a client protein for heat shock protein 90 (Hsp-90), whose overexpression is induced by photodynamic therapy (PDT), leading to the inhibition of capase-9 and the blockage of apoptosis. The overexpression of Hsp-90 in cancer cells can rapidly acquire thermoresistance during photothermal therapy (PTT), leading to insufficient apoptosis, increased cell viability, and tumor recurrence. A potential approach to block the PTT-induced overexpression of Hsp-90 and the overexpression of survivin is developed by using an Hsp-90 inhibitor and anticancer agent, namely, geldanamycin (GM). These inhibitors also develop a mild-temperature PTT strategy to reach synergistic PDT and PTT efficiency. Thus, Cy7-SQ is designed by a covalent disulfide linkage between a photothermal agent (i.e., canine dye 7 [Cy7]) and a photosensitizer (i.e., squaraine dye [SQ]) for the improved photostability and thermal stability of Cy7 and SQ. The cleavage of the Cy7-SQ linkage by glutathione in a tumor microenvironment increases the efficiency of synergistic PDT and PTT. In the current study, bovine serum albumin (BSA)/Cy7-SQ/GM nanoparticles are developed through the self-assembly of BSA, Cy7-SQ, and GM to accelerate the apoptosis of cancer cells via near-infrared (NIR) laser irradiation, thus realizing Hsp-90-regulated synergistic PDT/PTT combined with chemotherapy.
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http://dx.doi.org/10.1016/j.jcis.2021.01.052DOI Listing
May 2021

Nanoscale photosensitizer with tumor-selective turn-on fluorescence and activatable photodynamic therapy treatment for COX-2 overexpressed cancer cells.

J Mater Chem B 2021 03;9(8):2001-2009

Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Shaanxi 712100, P. R. China.

Effective targeting and in situ imaging-guided treatment are particularly important for accurate clinical photodynamic therapy (PDT) of malignant tumors. Herein, we propose a single molecule, named IMC-DAH-SQ, which possesses dual-targeting components, including structure-inherent targeting (SIT) and cyclooxygenase-2 (COX-2) targeting units, and controllable turn-on near infrared (NIR) fluorescence. Due to its amphiphilicity, IMC-DAH-SQ assembles into a nanoprobe with low background fluorescence. After incubation with tumor cells, the SIT and COX-2 recognition characteristics of IMC-DAH-SQ endow it with preferential tumor-targeting activity. The strong binding with overexpressed COX-2 can collapse the nanoprobe to monomers after accumulation in tumor cells, leading to turn-on NIR fluorescence that is completely different from normal cells. Additionally, benefiting from the single molecular model tactic, the nanoprobe has the advantages of simple synthesis without ever considering the loading rate and separation between the photosensitizer and targeting unit. Other favorite features, including superior biocompatibility, weak dark toxicity, and mitochondria enrichment capability, are implemented. All these traits not only afford nanoprobe precision tumor cell targeting capability but also provide promising imaging-guided antitumor therapy. We believe that the single molecular protocol will establish a novel strategy for simultaneous diagnosis and anticancer medicine treatment utilizing versatile but small compounds.
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http://dx.doi.org/10.1039/d0tb02828bDOI Listing
March 2021

Hsa_circ_0025202 suppresses cell tumorigenesis and tamoxifen resistance via miR-197-3p/HIPK3 axis in breast cancer.

World J Surg Oncol 2021 Feb 3;19(1):39. Epub 2021 Feb 3.

Department of Laboratory Medicine, Jingmen No.1 People's Hospital, Jingmen, 448000, Hubei, China.

Background: The involvement of circular RNAs (circRNAs) in tamoxifen (TAM) resistance has been identified. Herein, we aimed to identify the role and novel mechanisms of hsa_circ_0025202 in tamoxifen resistance in breast cancer (BC).

Methods: The levels of hsa_circ_0025202, microRNA (miR)-197-3p, and homeodomain-interacting protein kinase 3 (HIPK3) were tested using quantitative real-time polymerase chain reaction and western blot. IC value of TAM, cell proliferation, cell cycle, cell invasion, migration, apoptosis, western blot, and mouse xenograft assays was used to demonstrate the effects of hsa_circ_0025202, miR-197-3p, and HIPK3 on BC cell tumorigenesis and TAM resistance. Dual-luciferase report and RNA immunoprecipitation assays were applied to explore the potential interaction between miR-197-3p and hsa_circ_0025202 or HIPK3.

Results: Hsa_circ_0025202 was decreased in BC tissues and TAM resistant BC cells, and knockdown of hsa_circ_0025202 elevated the IC value of cells to TAM, led to the promotion of cell proliferation, invasion and migration, mediated cell cycle progression, and inhibited cell apoptosis in BC in vitro. Besides, the upregulation of hsa_circ_0025202 hindered tumor growth and promoted TAM sensitivity in vivo. In a mechanical study, hsa_circ_0025202 targeted miR-197-3p, and silencing of miR-197-3p reversed the regulatory effects of hsa_circ_0025202 knockdown on TAM resistance and malignant phenotypes. Additionally, HIPK3 was a target of miR-197-3p, and miR-197-3p overexpression enhanced TAM resistance and promoted cell malignant biological behaviors in BC by targeting HIPK3.

Conclusion: Hsa_circ_0025202 repressed cell tumorigenesis and TAM resistance via miR-197-3p/HIPK3 axis in BC, suggesting a potential therapeutic strategy to overcome chemoresistance in BC patients.
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http://dx.doi.org/10.1186/s12957-021-02149-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860040PMC
February 2021

Down-regulation of MALAT1 aggravates polycystic ovary syndrome by regulating MiR-302d-3p-mediated leukemia inhibitory factor activity.

Life Sci 2021 Jan 16;277:119076. Epub 2021 Jan 16.

Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450000, PR China. Electronic address:

Aims: Accumulating evidence have shown the important roles of long noncoding RNA (lncRNA) in controlling different diseases. In the present study, we tried to explore the role which lncRNA MALAT1 plays in polycystic ovary syndrome (PCOS) with the involvement of microRNA-302d-3p (miR-302d-3p) and leukemia inhibitory factor (LIF).

Methods: A PCOS rat model was established and characterized, followed by treatment with si-MALAT1, oe-MALAT1, miR-302d-3p mimic, or miR-302d-3p inhibitor constructs. Serum hormonal levels were detected to evaluate endocrine conditions. The effect of MALAT1 and miR-302d-3p on activities of ovarian granulosa cells was assessed, as well as the involvement of LIF.

Results: MALAT1 expression was shown to be downregulated in ovarian tissue of PCOS rats. Overexpression of MALAT1 in vitro promoted proliferation and inhibited apoptosis of ovarian granulosa cells. Overexpression of MALAT1 in vivo reduced the ovarian tissue injury and endocrine disorders accompanied with decreased level of FSH and elevated serum levels of E2, T, and LH in the PCOS rat. Overexpression of MALAT1 also promoted the expression of LIF, which could be reversed by overexpression of miR-302d-3p, indicating that MALAT1 up-regulated the expression of LIF via miR-302d-3p. Furthermore, overexpression of MALAT1 reduced endocrine disorders and ovarian tissue damage via the miR-302d-3p/LIF axis.

Conclusion: Our study highlighted that MALAT1 plays a protective role in reducing ovarian tissue damage and endocrine disorder in PCOS by regulating the miR-302d-3p/LIF axis.
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http://dx.doi.org/10.1016/j.lfs.2021.119076DOI Listing
January 2021

Comparison of outcomes between endoscopic and microscopic transsphenoidal surgery for the treatment of pituitary adenoma: a meta-analysis.

Gland Surg 2020 Dec;9(6):2162-2174

The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China.

Background: Pituitary tumors are among the most common intracranial tumors. Surgical resection is the most effective treatment for patients with pituitary tumors. Microscopic transsphenoidal surgery has become the first-choice surgical approach to treating this malignancy, although it has certain limitations. Neuroendoscopy has also been widely used for pituitary tumor surgery in recent years. This study aimed to compare the efficacy and safety of these two surgical options for the treatment of pituitary tumors.

Methods: We conducted a literature search of the PubMed, Embase, Cochrane Controlled Center Register of Controlled Trials (CENTRAL), Web of Science database, Google Scholar, and Baidu Scholar. Relevant articles published up to September 25, 2020 were retrieved and then meta-analyzed using RevMan software 5.1.

Results: A total of 29 case-control studies involving 7,774 patients were included in the meta-analysis. There was no significant difference in gross tumor removal (GTR) (RR =1.11, 95% CI: 0.97-1.26, P=0.12) or hormone excess secretion (HES) remission (RR =1.08, 95% CI: 0.97-1.21, P=0.16) between the two groups. Endoscopic transsphenoidal surgery was associated with a lower incidence of diabetes insipidus (DI) than was microscopic transsphenoidal surgery (RR =0.76, 95% CI: 0.60-0.97, P=0.03).

Conclusions: Endoscopic transsphenoidal surgery does not significantly improve GTR or HES remission, but it can reduce the incidence of DI without increasing the rates of other complications.
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http://dx.doi.org/10.21037/gs-20-851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804537PMC
December 2020

The effects of vitamin D supplementation on glycemic control and maternal-neonatal outcomes in women with established gestational diabetes mellitus: A systematic review and meta-analysis.

Clin Nutr 2020 Dec 21. Epub 2020 Dec 21.

Department of Preventive Medicine, Hangzhou Normal University School of Medicine, Hangzhou, 311121, China. Electronic address:

Background & Aims: Gestational Diabetes Mellitus (GDM) is associated with a well-documented range of adverse pregnancy outcomes. The present meta-analysis was conducted to evaluate the effects of vitamin D supplementation on glycemic control and maternal-neonatal outcomes in women with established GDM.

Methods: Published literature was retrieved and screened from PubMed, Embase, Web of Science, CNKI (China National Knowledge Infrastructure), Wanfang, and Cochrane Center Register of Controlled Trails up to May 2020. RCTs of vitamin D supplementation on pregnant women with GDM were included.

Results: 19 RCTs (1550 participants) were eligible for meta-analyses. Overall, vitamin D supplementation significantly reduced serum fasting plasma glucose (FPG) (MD: -10.20 mg/dL, 95%CI: -13.43 to -6.96), insulin concentration (MD: -5.02 μIU/mL, 95%CI: -6.83 to -3.20) and the homeostasis model assessment of insulin resistance (HOMA-IR) (MD:-1.06, 95%CI: -1.40 to -0.72) in women with GDM. In addition, vitamin D supplementation in pregnant women with GDM significantly reduced adverse maternal outcomes including cesarean section (RR: 0.75, 95%CI: 0.63 to 0.89), maternal hospitalization (RR: 0.13, 95%CI: 0.02 to 0.98) and postpartum hemorrhage (RR: 0.47, 95%CI: 0.22 to 1.00). Several adverse neonatal complications including neonatal hyperbilirubinemia (RR: 0.47, 95%CI: 0.33 to 0.67), giant children (RR: 0.58, 95%CI: 0.38 to 0.89), polyhydramnios (RR: 0.42, 95% CI: 0.24 to 0.72), fetal distress (RR: 0.46, 95%CI: 0.24 to 0.90) and premature delivery (RR: 0.43, 95% CI: 0.26 to 0.72) were also significantly reduced.

Conclusions: This meta-analysis suggested that supplementation of GDM women with vitamin D may lead to an improvement in glycemic control and reduction of adverse maternal-neonatal outcomes.
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http://dx.doi.org/10.1016/j.clnu.2020.12.016DOI Listing
December 2020

Clinical Correlation of Wnt2 and COL8A1 With Colon Adenocarcinoma Prognosis.

Front Oncol 2020 28;10:1504. Epub 2020 Aug 28.

Department of Oncology, Affiliated Hospital of Jiangnan University, Wuxi, China.

Wnt2 mRNA is widely expressed in various tumor tissues. Wnt2 overexpression promotes tumor growth, migration, invasion, and metastasis. However, its underlying molecular action mechanisms and clinical implications in colon adenocarcinoma (COAD) remain unclear. mRNA expression data, obtained from tissue samples, and pathophysiological data of 368 COAD patients were obtained from the Cancer Genome Atlas (TCGA) database. Further, Pearson's correlation analysis was performed to explore the correlation between the expression levels of Wnt2 and other genes in the human genome. Subsequently, a protein-protein interaction (PPI) network was constructed for hub gene identification. Overall survival and significance were determined by Kaplan-Meier analysis, and the log-rank test was used to further identify genes with prognostic significance in COAD from GEO datasets (GSE17538 and GSE39582). Subsequently, 158 tissue samples from Affiliated Hospital of Jiangnan University were used for expression verification. Gene set enrichment analysis (GSEA) was performed on high and low Wnt2 expression datasets to identify potential signaling pathways activated in COAD. In all, 10 hub genes associated with Wnt2 were screened by Pearson's correlation analysis and PPI network, with Wnt2 and COL8A1 having significantly poor prognosis by Kaplan-Meier analysis and log-rank test. Furthermore, high expressions of COL8A1 and Wnt2 were associated with poor survival both in TCGA and GEO cohorts. We further found a correlation between the expressions of Wnt2 and COL8A1 in COAD as per immunohistochemical analysis. To further elucidate the underlying molecular mechanisms of Wnt2 in COAD, we searched for pathways enriched in Wnt2 overexpressing datasets by GSEA. Our findings revealed that high Wnt2 levels were significantly associated with extracellular matrix receptor and focal adhesion pathways. Wnt2 expression correlated with COL8A1 expression in COAD; patients with high Wnt2 and COL8A1 expressions had worse survival outcomes. Pathways identified in this study prompt the molecular role of Wnt2 in COAD and provide directions to further elucidate the involved molecular mechanisms in COAD.
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http://dx.doi.org/10.3389/fonc.2020.01504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484937PMC
August 2020

Clinical significance of dysregulation of miR-381 in pediatric acute myeloid leukemia.

Eur J Med Res 2020 Sep 16;25(1):42. Epub 2020 Sep 16.

Department of Pediatrics, Linyi People Hospital, No. 27, East Jiefang Road, Linyi, 276003, Shandong, China.

Background: microRNA-381 is dysregulated in a variety of cancers. However, its clinical significance in pediatric acute myeloid leukemia (AML) is still unclear. The purpose of this study was to detect the expression level of miR-381 in pediatric AML patients and to explore its potential clinical significance.

Methods: The levels of miR-381 in bone marrow and serum of 102 pediatric AML patients were measured by quantitative real-time polymorperase chain reaction (qRT-PCR). The diagnostic value of serum miR-381 in pediatric AML patients was evaluated by the receiver operating characteristic (ROC) curve. A Chi square test was used to analyze the relationship between serum miR-381 and the clinical characteristics of patients. Cox regression analysis and Kaplan-Meier evaluated the prognostic value of serum miR-381 in patients. Finally, the proliferation of the cells was analyzed by the CCK-8 assay.

Results: Compared with healthy controls, the levels of miR-381 in serum and bone marrow of pediatric AML patients were significantly decreased (P < 0.001). ROC curve showed that miR-381 could distinguish pediatric AML cases from normal controls. At the same time, the downregulation of miR-381 was associated with M7 in the French-American-British (FAB) classifications and unfavorable cytogenetic risks (P < 0.05). Low serum miR-381 levels were associated with poor overall survival of pediatric AML (log-rank test, P = 0.011) and poor relapse-free survival (log-rank test, P = 0.004). Cox regression analysis confirmed that reduced serum miR-381 was an independent predictor of poor prognosis in AML (HR = 3.794, 95% CI 1.3633-10.559, P = 0.011). In addition, low expression of miR-381 significantly reduced the proliferation of cells (P < 0.05).

Conclusion: All experimental results confirm that miR-381 has reduced bone marrow and serum expression in pediatric AML, and low levels of serum miR-381 have certain diagnostic and prognostic value in pediatric AML and may be a potential therapeutic target for AML.
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http://dx.doi.org/10.1186/s40001-020-00442-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493963PMC
September 2020

The effect of traditional Tibetan guozhuang dance on vascular health in elderly individuals living at high altitudes.

Am J Transl Res 2020 15;12(8):4550-4560. Epub 2020 Aug 15.

Institute of Geriatric, Qinghai Provincial People's Hospital Xining, People's Republic of China.

To evaluate the effect of dance on vascular-related factors and cerebral hemodynamics in elderly individuals in Qinghai-Tibetan plateau regions (mean altitude ≥2,300 m). Thirty elderly individuals, who practiced traditional Tibetan Guozhuang dance or did not, were enrolled, respectively. Serum PGC-1α, HCY, FSTL-1, VEGF and HIF-1α were measured by ELISA assays. Carotid artery stenosis and plaque, IMT, extracranial internal carotid artery stenosis and cerebral arteriosclerosis were evaluated using CUS and TCD. Body weight, BMI, heart rate, systolic pressure, and diastolic pressure, serum BGS, TC, LDL, HIF-1α, VEGF, and HCY in the dance group were significantly lower than the no-dance group. FSTL-1 levels, SO and SO/heart rate ratio in the dance group were significantly higher than the no-dance group. Incidence of extracranial internal carotid artery stenosis, carotid stenosis and plaque in the dance group was significantly lower than the no-dance group. IMT was a significant positive correlation between PGC-1α and HCY in the no-dance group. Elderly individuals who regularly practiced Tibetan dance had improved blood vessel functionality and cerebral hemodynamic at high altitudes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476110PMC
August 2020

Interplay of microRNAs to genetic, epigenetic, copy number variations of cervical cancer related genes.

J Reprod Immunol 2020 11 8;142:103184. Epub 2020 Aug 8.

Department of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan, 450007, China. Electronic address:

This study was to analyses the miRNAs role in cervical cancer and possibilities of microRNA-based markers as diagnostic tools. Genome wide analysis was performed for CNV detection using PennCNV and QuantiSNP. The associated mRNA qRT-PCR detection was used to measure quantities of microRNA gene expression. More than 10 CNV regions has a significant relationship with cervical cancer risk for both CNV detection algorithms. A total of 34 CNVs was detected by QuantiSNP while it was 27 in case of PennCNV, among which 22 CNVs was found to be overlapping between these two algorithms. the mRNA was analyzed for its expression on 36 carvical tumor normal tissue pairs of four targets i.e., MAP3K3, RIPK2, DIRAS3 and GAS7. These infers that there was a significant downregulation of all the four genes cervical tumor. Our results showed that miR-182 can modulate the expression of FAM83H, DIRAS3, RIPK2 and MAP3K3 in cervical cancer. Therefore, indicated that miR-182 can acts through these signaling pathway in proliferation of cervical cancer cells. The expression of tumor modulator miRNAs can be controlled by miRNA replacement therapy. Several miRNAs have been used for this purpose. The modulation of various signaling pathway and proteins in cervical cancer cells by miR-182 needs further clarification.
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http://dx.doi.org/10.1016/j.jri.2020.103184DOI Listing
November 2020

MicroRNA-191 modulates cisplatin-induced DNA damage response by targeting RCC2.

FASEB J 2020 10 16;34(10):13573-13585. Epub 2020 Aug 16.

Department of Preventive Medicine, Hangzhou Normal University School of Medicine, Hangzhou, China.

Cisplatin is a first-line chemotherapeutic agent for the treatment of many types of cancer, but the emergence of chemoresistance hinders its application. Thus, a better understanding of cisplatin-induced DNA damage response (DDR) would help to overcome this problem. Previously, we have identified a panel of microRNAs with altered expression after cisplatin treatment in HeLa cells. In the current study, we focused on one of them, miR-191, and investigated its function in cisplatin-induced DDR. We found that overexpression of miR-191 sensitized HeLa cells to the cytotoxic effects of cisplatin, resulted in decreased viable cells. However, overexpression of miR-191 did not cause changes in apoptotic cell ratio but rather induced significant G2/M arrest in HeLa cell treated with cisplatin. Additionally, enhanced cisplatin-induced DNA damage was observed. Through bioinformatic analysis and verified by dual-luciferase assay, it was demonstrated that the chromosome condensation 2 regulator (RCC2) gene is a target for miR-191 regulation. Furthermore, the downregulation of RCC2 by siRNA mimics the effects of miR-191, in which greater DNA damage was observed upon cisplatin treatment. Taken together, our study indicates that miR-191 may be an important player in cisplatin-induced DDR, and it elicits its function, at least partially, through the regulation of RCC2.
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http://dx.doi.org/10.1096/fj.202000945RDOI Listing
October 2020

Product-boosted fluorescence signal: a new approach for designing small-molecule probes for detection of peroxynitrite.

Chem Commun (Camb) 2020 Jul 12;56(57):7925-7928. Epub 2020 Jun 12.

Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Shaanxi 712100, P. R. China.

In situ self-assembled boronate ester comprising commercially available 2-formylphenylboronic acid and 2-(2',3'-bihydroxyphenyl)benzothiazole (BHBT) is explored for the detection of ONOO with product-boosted fluorescence. The self-assembly can detect ONOO in the endoplasmic reticulum of living cells.
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http://dx.doi.org/10.1039/d0cc02963gDOI Listing
July 2020

Herbal medicine significantly improved muscle function in a patient with type 1 facioscapulohumeral muscular dystrophy: A case report.

Explore (NY) 2021 May-Jun;17(3):247-251. Epub 2020 May 24.

The First Comprehensive Department, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Province Hospital of Chinese Medicine), Guangzhou, Guangdong, 510120, China. Electronic address:

Background And Aim: Facioscapulohumeral muscular dystrophy (FSHD) is a common muscular disorder. At present, treatments for FSHD have limited effects on the muscle function of patients. A famous Chinese medicine formula, Buzhong Yiqi (BZYQ), has shown promising effects on several muscular diseases, but evidence regarding its effect on FSHD is lacking. This study aimed to examine the effect of BZYQ on FSHD.

Case Presentation: A 15-year-old girl suffered from progressive muscle weakness, with a genetically confirmed diagnosis of FSHD. Except for routine FSHD management, the patient received BZQY every day. The muscle strength of the patient remarkably increased after discharge.

Conclusions: This study was novel in reporting a significant improvement in muscle function in a patient with FSHD treated with an integrated approach of BZYQ and routine management. Therefore, BZYQ might be a potential treatment for FSHD, requiring further investigations.
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http://dx.doi.org/10.1016/j.explore.2020.05.009DOI Listing
May 2020

Width-Consistent Mesoporous Silica Nanorods with a Precisely Controlled Aspect Ratio for Lysosome Dysfunctional Synergistic Chemotherapy/Photothermal Therapy/Starvation Therapy/Oxidative Therapy.

ACS Appl Mater Interfaces 2020 Jun 19;12(22):24611-24622. Epub 2020 May 19.

Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Xinong Road 22, Yangling, Shaanxi 712100, China.

Although differently shaped mesoporous silica is widely studied, the formation of width-consistent mesoporous silica nanorods (MSNRs) with a precisely controlled aspect ratio (AR: length/width) is challenging and has not been reported. Herein, width-consistent (100 nm) MSNRs with ARs of 2, 3, 4, 6, 8, and 10 were obtained by increasing the concentrations while maintaining the molar ratio of cetyltrimethylammonium bromide (CTAB) and tetraethyl orthosilicate (TEOS). The results demonstrated that the as-prepared MSNR with an AR of 6 (AR6) possesses high cellular-uptake efficiency and drug-loading capacity. Thus, AR6-based cancer-cell-targeting nanosystems were designed. These nanosystems encapsulated doxorubicin (DOX) into the porous channel of AR6, adsorbed glucose oxidase (GOx), and then formed a polydopamine (PDA) layer for Siramesine (Siram, a lysosome dysfunctional drug) adsorption and folic acid modification. In this design, the PDA shell could prevent the leakage of loading components and keep the activity of GOx during delivery while achieving an on-demand drug release in the targeted location and photothermal therapy under near-infrared irradiation. The increase in temperature was highly beneficial for elevating the catalytic efficiency of GOx, accelerating the consumption of intracellular glucose, and generating a relatively high level of cytotoxic HO, all of which enhanced starvation and oxidative therapies. Siram was employed to inhibit lysosomal metabolism and accompany GOx to reach a dual-enhanced starvation therapy effect. In addition, DOX entered the nucleus and altered DNA for chemotherapy. The results showed that the nanosystems have superior therapeutic efficacy against cancer cells and not much toxicity to normal cells. Therefore, this study provides a novel strategy for lysosome dysfunctional synergistic chemotherapy/photothermal therapy/starvation therapy/oxidative therapy based on MSNR.
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http://dx.doi.org/10.1021/acsami.0c06117DOI Listing
June 2020

Cyanide Boosting Copper Catalysis: A Mild Approach to Fluorescent Benzazole Derivatives from Nonemissive Schiff Bases in Biological Media.

Org Lett 2020 05 10;22(9):3361-3366. Epub 2020 Apr 10.

Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Shaanxi 712100, P. R. China.

An application of nucleophilic cyclization and oxidation of nonemissive Schiff bases via cyanide boosting copper catalysis to synthesize fluorescent benzazole derivatives in high conversion yield is disclosed. This approach is highlighted by broad substrate scope, fast reaction time, and mild conditions and can efficiently proceed in living cells or root tissues. Furthermore, this methodology can be applied for selective detection of Cu and CN.
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http://dx.doi.org/10.1021/acs.orglett.0c00784DOI Listing
May 2020

Sphingosine 1-phosphate promotes the proliferation of olfactory ensheathing cells through YAP signaling and participates in the formation of olfactory nerve layer.

Glia 2020 09 14;68(9):1757-1774. Epub 2020 Feb 14.

Department of Orthopedics (Spine Surgery), Wenzhou Medical University First Affiliated Hospital, Wenzhou, Zhejiang, China.

Olfactory ensheathing cells (OECs) are unique glial cells with axonal growth-promoting properties in the olfactory epithelium and olfactory bulb, covering the entire length of the olfactory nerve. The proliferation of OECs is necessary for the formation of the presumptive olfactory nerve layer (ONL) during development and OECs transplantation. However, the molecular mechanism underlying the regulation of OEC proliferation in the ONL still remains unknown. In the present study, we examined the role of sphingosine 1-phosphate (S1P) and S1P receptors (S1PRs) on OEC proliferation. Initially, reverse transcription-PCR (RT-PCR), western blot and immunostaining revealed that S1PRs were highly expressed in the OECs in vitro and in vivo. Furthermore, we found that S1P treatment promoted the proliferation of primary cultured OECs mediated by S1PR1. Mechanistically, yes-associated protein (YAP) was required for S1P-induced OEC proliferation through RhoA signaling. Finally, conditional knockout of YAP in OECs reduced OEC proliferation in ONL, which impaired the axonal projection and growth of olfactory sensory neurons, and olfactory functions. Taken together, these results reveal a previously unrecognized function of S1P/RhoA/YAP pathway in the proliferation of OECs, contributing to the formation of ONL and the projection, growth, and function of olfactory sensory neurons during development.
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http://dx.doi.org/10.1002/glia.23803DOI Listing
September 2020

Effect of 3-Aminobenzamide on the Ultrastructure of Astrocytes and Microvessels After Focal Cerebral Ischemia in Rats.

Dose Response 2020 Jan-Mar;18(1):1559325819901242. Epub 2020 Jan 22.

Department of Rehabilitation Medicine, The First People's Hospital of Wenling, Wenzhou Medical University, Wenling, Zhejiang, China.

The disruption of blood-brain barrier (BBB) is a critical event in the formation of brain edema during early phases of ischemic brain injury. Poly(ADP-ribose) polymerase (PARP) activation, which contributes to BBB damage, has been reported in ischemia-reperfusion and traumatic brain injury. Here, we investigated the effect of 3-aminobenzamide (3-AB), a PARP-1 inhibitor, on the ultrastructure of BBB. Male Sprague Dawley rats were suffered from 90 minutes of middle cerebral artery occlusion, followed by 4.5 hours or 22.5 hours of reperfusion (R). The vehicle or 3-AB (10 mg/kg) was administered intraperitoneally (ip) 60 minutes after lacking of blood. Tissue Evans Blue (EB) levels, ultrastructures of astrocytes and microvessels, and areas of perivascular edema were examined in penumbra and core, at I 1.5 hours /R 4.5 hours and I 1.5 hours /R 22.5 hours, respectively. The severity of ultrastructural changes was graded with a scoring system in each group. We showed that 3-AB treatment significantly decreased tissue EB levels and ultrastructural scores, attenuated damages in astrocytes and microvessels, and reduced areas of perivascular edema. In conclusion, PARP inhibition may provide a novel therapeutic approach to ischemic brain injury.
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http://dx.doi.org/10.1177/1559325819901242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977239PMC
January 2020

A novel fluorescent probe based on naphthalimide for imaging nitroreductase (NTR) in bacteria and cells.

Bioorg Med Chem 2020 02 24;28(3):115280. Epub 2019 Dec 24.

Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Xinong Road 22, Yangling, Shaanxi 712100, PR China. Electronic address:

A nitroreductase (NTR) responsive fluorescent probe, Na-NO, comprising p-nitrobenzyl as the unique recognition group and 1,8-naphthalimide as fluorophore, was synthesized. Na-NO showed remarkable fluorescence "turn-on" signal in the presence of NTR under DMSO/HO (1:19, v/v) buffered with PBS (pH = 7) solution in the presence of NADH (300 µM). Furthermore, the probe has a low detection limit down to 3.4 ng/mL and it is very sensitive towards the NTR in Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), normal and tumor cells such as HL-7702, HepG-2 and MCF-7.
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http://dx.doi.org/10.1016/j.bmc.2019.115280DOI Listing
February 2020

Comparison of backslopping and two-stage fermentation methods for koumiss powder production based on chemical composition and nutritional properties.

J Sci Food Agric 2020 Mar 10;100(4):1822-1826. Epub 2020 Jan 10.

State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Science and Engineering, Tianjin University of Science and Technology, Tianjin, China.

Background: Koumiss is a traditional fermented beverage made from mare's milk. The traditional backslopping method for koumiss production has shortcomings in terms of microbiological diversity and nutritional characteristics. In this study, a two-stage fermentation method was established to scale up the production of koumiss powder. The chemical composition and nutritional properties of a novel two-stage fermentation koumiss powder (TKP) were compared with backslopping koumiss powder (BKP).

Results: The TKP exhibited important nutritional and functional properties, including a high percentage of essential amino acids, and high polyunsaturated fatty acid, vitamin, and mineral content. The essential amino acid content of TKP was not significantly different from that of BKP. The oleic acid, linoleic acid, linolenic acid, and water-soluble vitamin content of TKP was higher than that of BKP. The Ca:P ratio of TKP was also close to the optimal Ca:P ratio in humans.

Conclusion: The novel method could be applied for the scaled-up production of koumiss powder with similar nutritional properties to traditional backslopping koumiss powder. The successful production of koumiss powder could also promote the development of the koumiss industry. © 2019 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.10220DOI Listing
March 2020

Isolation and Detection Technologies of Extracellular Vesicles and Application on Cancer Diagnostic.

Dose Response 2019 Oct-Dec;17(4):1559325819891004. Epub 2019 Dec 9.

Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, USA.

The vast majority of cancers are treatable when diagnosed early. However, due to the elusive trace and the limitation of traditional biopsies, most cancers have already spread widely and are at advanced stages when they are first diagnosed, causing ever-increasing mortality in the past decades. Hence, developing reliable methods for early detection and diagnosis of cancer is indispensable. Recently, extracellular vesicles (EVs), as circulating phospholipid vesicles secreted by cells, are found to play significant roles in the intercellular communication as well as the setup of tumor microenvironments and have been identified as one of the key factors in the next-generation technique for cancer diagnosis. However, EVs present in complex biofluids that contain various contaminations such as nonvesicle proteins and nonspecific EVs, resulting in the interference of screening for desired biomarkers. Therefore, applicable isolation and enrichment methods that guarantee scale-up of sample volume, purity, speed, yield, and tumor specificity are necessary. In this review, we introduce current technologies for EV separation and summarize biomarkers toward EV-based cancer liquid biopsy. In conclusion, a novel systematic isolation method that guarantees high purity, recovery rate, and tumor specificity is still missing. Besides that, a dual-model EV-based clinical trial system includes isolation and detection is a hot trend in the future due to efficient point-of-care needs. In addition, cancer-related biomarkers discovery and biomarker database establishment are essential objectives in the research field for diagnostic settings.
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http://dx.doi.org/10.1177/1559325819891004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902397PMC
December 2019

UGT1A1*28 gene polymorphism was not associated with the risk of neonatal hyperbilirubinemia: a meta-analysis.

J Matern Fetal Neonatal Med 2019 Dec 25:1-8. Epub 2019 Dec 25.

Department of Pediatrics, Linyi People's Hospital, Linyi, China.

This study aimed to evaluate the relationship between UGT1A1*28 gene polymorphism and the risk of neonatal hyperbilirubinemia (NHBI). The studies meet certain selection condition which was obtained from databases such as PubMed, Embase, and Cochrane Library. Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of included studies. Meta-analysis was performed according to criteria such as country. Hardy-Weinberg's equilibrium (HWE) tests were performed on the control group using chi-square test, while the evaluation index was represented by odds ratio (OR) and 95% confidence interval (CI). Egger's test and sensitivity analysis were used to evaluate the publication bias and reliability, repetitively. Totally, four studies with high overall quality were enrolled in this study. No association was observed between UGT1A1*28 gene polymorphisms and NHBI in allele model (TA7 versus TA6, OR (95% CI) = 2.13 (0.81-5.62),  = .13), codominance models (TA7/6 versus TA6/6, OR (95% CI) = 2.94 (0.90-9.57),  = .07; TA7/7 versus TA6/6, OR (95% CI) = 2.08 (0.37-11.52),  = .40), recessive model (TA7/7 versus TA6/6 + TA7/6, OR (95% CI) = 1.44 (0.41-5.14),  = .57), and dominant model (TA7/7 + TA7/6 versus TA6/6, OR (95% CI) = 2.92 (0.84-10.12),  = .09). Furthermore, there was no publication bias found in current meta-analysis. Gene polymorphism of UGT1A1*28 might not be associated with the risk of NHBI.
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http://dx.doi.org/10.1080/14767058.2019.1702962DOI Listing
December 2019

Mixed probiotics decrease the incidence of stage II-III necrotizing enterocolitis and death: A systematic review and meta-analysis.

Microb Pathog 2020 Jan 28;138:103794. Epub 2019 Oct 28.

Department of Prevention Medicine, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China. Electronic address:

Background: Necrotizing enterocolitis (NEC) is a major cause of morbidity and mortality in premature infants. In order to evaluate the efficacy of probiotics in the prevention of stage II-III NEC, we performed a meta-analysis of clinical studies.

Methods: We searched in PubMed, Medline and Embase from 1 January 1990 to 16 January 2018. Heterogeneity was examined by Q-test. Publication bias was evaluated by funnel plot and Egger's regression test.

Results: 30 articles were identified meeting the inclusion criteria. Data showed that probiotics supplement could significantly reduce the risk of stage II-III NEC (RR = 0.51, 95% CI, 0.38 to 0.67, P < 0.001) and death rate (RR = 0.69, 95% CI, 0.55 to 0.87, P = 0.002). The mixed probiotics and lactobacillus could reduce the risk of stage II-III NEC (for mixed probiotics, RR = 0.39, 95% CI, 0.26 to 0.57; for lactobacillus, RR = 0.53, 95% CI, 0.36 to 0.78), while bifidobacterium or saccharomyces did not have such effect. The results also indicated that only the mixed probiotics could reduce the risk of deaths (RR = 0.52, 95%CI, 0.34 to 0.80). Subgroup analysis for mortality revealed that probiotics had significant effect in Asian region (RR = 0.54, 95% CI, 0.37 to 0.80, P = 0.002) but not in non-Asian region (RR = 0.84, 95% CI, 0.66 to 1.08, P = 0.179).

Conclusions: Probiotics could significantly decrease the risk of stage II-III NEC and death. Compared to using single probiotics species, the application of combining different probiotics has a better efficacy in the prevention of stage II-III NEC and death, especially in the Asian population.
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http://dx.doi.org/10.1016/j.micpath.2019.103794DOI Listing
January 2020

Transcription factor Six2 induces a stem cell-like phenotype in renal cell carcinoma cells.

FEBS Open Bio 2019 10 19;9(10):1808-1816. Epub 2019 Sep 19.

Department of Pediatric Nephrology and Rheumatism and Immunology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.

Renal cell carcinoma (RCC) accounts for 2-3% of adult malignant tumors, and the incidence of RCC worldwide has increased by about 2% over the past two decades. The homeobox protein Six2 has been shown to promote the stemness of breast cancer cells and play a role in kidney development, but its involvement in RCC progression has not previously been investigated. Here, we found that six2 expression was significantly increased in RCC tissues and negatively correlated with the overall survival of patients with RCC. In addition, six2 expression exhibited a remarkably higher level relative to that in normal renal cells. Functional experiments showed that six2 knockdown attenuated the stemness of RCC cells, which was evident by decreased spheroid formation ability and stemness marker (sox2 and nanog) expression. Mechanistic studies indicated that Six2 directly bound to the enhancer of sox2, promoting sox2 expression and downstream effector expression of nanog. Furthermore, overexpression of sox2 rescued the inhibitory effects of six2 on the stemness of RCC cells. Notably, six2 expression is positively correlated with sox2 and nanog expression in RCC tissues. Collectively, our results point toward a six2/sox2 axis responsible for RCC cell stemness.
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http://dx.doi.org/10.1002/2211-5463.12721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768107PMC
October 2019

Autoimmune Lymphoproliferative Syndrome with Cryptococcus Infection.

J Clin Immunol 2019 10 11;39(7):747-749. Epub 2019 Aug 11.

Department of Pediatrics, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated with Shandong First Medical University, Shandong University, 16766 Jingshi Road, Jinan, 250014, China.

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http://dx.doi.org/10.1007/s10875-019-00676-7DOI Listing
October 2019

Recent development in biodegradable nanovehicle delivery system-assisted immunotherapy.

Biomater Sci 2019 Nov 31;7(11):4414-4443. Epub 2019 Jul 31.

Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Shaanxi 712100, P. R. China.

Based on the stimulation of the patient's own innate and adaptive immunity, immunotherapy is used in tumor treatment, and in recent years, it has developed rapidly. To generate strong and long-lasting antitumor immune responses and to boost clinical efficiency, various nanovehicle delivery systems (NDSs) have been designed to achieve specific release and avoid premature leakage in the delivery process. However, most of them are nondegradable, and they are taken up by the liver and spleen. This process leads to the accumulation of these substances in the human body, raising long-term toxicity concerns and causing potential undesirable side effects. To solve this problem, biodegradable NDSs (BNDSs) have been developed. Once these substances reach their target, they can only be degraded under specific internal or external stimuli, such as enzymes, irradiation, temperature, redox potential, pH, or a combination of these stimuli. Therefore, they are quite significant for potential clinical applications. In this review article, we highlight the recent literature on the design and working mechanism of various BNDSs. According to their type and characteristics, BNDSs are categorized as follows: (1) polymers, (2) lipid based materials, (3) inorganic nanomaterials, (4) biomacromolecules, (5) hybrid materials and (6) other materials. The existing challenges and future prospects of these materials will also be discussed.
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http://dx.doi.org/10.1039/c9bm00961bDOI Listing
November 2019

Purification of spinosin from Ziziphi Spinosae Semen using macroporous resins followed by preparative high-performance liquid chromatography.

J Sep Sci 2019 Oct 14;42(19):3134-3140. Epub 2019 Aug 14.

School of Pharmacy, the Key Laboratory of Prescription Effect and Clinical valuation of State Administration of Traditional Chinese Medicine of China, Binzhou Medical University, Yantai, P. R. China.

As a well-known traditional Chinese medicine, Ziziphi Spinosae Semen has been used for treating anxiety and insomnia for a long time. Spinosin, the main active C-glycoside flavonoid in Ziziphi Spinosae Semen, has attracted much attention because of its many pharmacological activities including strong hypnotic effects, anxiolytic-like effects, and so on. In the present work, high-purity spinosin was separated from Ziziphi Spinosae Semen using the HPD-300 resin followed by preparative high-performance liquid chromatography. The adsorption kinetics curve of spinosin on the HPD-300 resin was studied and fitted well by the pseudo-second-order equation. The adsorption isotherms were also constructed and low temperature favored the adsorption reaction. The separation parameters were optimized using dynamic adsorption and desorption tests. After a one-run treatment with HPD-300 resin, the concentration of spinosin increased 11.8-fold from 0.99 to 11.7% with a recovery yield of 80.4%. Furthermore, the purity of spinosin could surpass above 98% after separation by preparative high-performance liquid chromatography and recrystallization with a recovery yield of 72.6%. The developed method was effective and suitable for the large-scale preparation of spinosin. Moreover, it was confirmed that HPD-300 resin could enable good selection for the enrichment of flavonoids from different plants.
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http://dx.doi.org/10.1002/jssc.201900433DOI Listing
October 2019

Trends in epilepsy diagnosis and surgery in western China during 2009-2017.

J Neurol Sci 2019 Aug 26;403:153-158. Epub 2019 Jun 26.

Neurology Department, West China Hospital, Sichuan University, Chengdu, China. Electronic address:

Objective: Despite the strong evidence for the efficacy of surgery to treat temporal lobe epilepsy, the number of such surgeries has plateaued in western countries. This study examined trends in the number of epilepsy cases diagnosed, number of surgeries performed, and certain characteristics of surgery patients in western China between January 2009 and December 2017.

Methods: Data were obtained for a population-based sample from a healthcare information system, as well as for a patient population from West China Hospital. Age at epilepsy onset, age at surgery, duration of epilepsy, and type of epilepsy pathology based on surgical samples were analyzed.

Results: Data were obtained for 14,710 hospitalizations from the healthcare system and 17,302 hospitalizations from West China Hospital. The number of hospitalizations, but not the number of epilepsy surgeries, increased during the study period. Patients' age at epilepsy onset, age at surgery or epilepsy duration did not change significantly during the study period.

Significance: Our analysis suggests that in western China, as in western countries, the number of temporal epilepsy surgeries has plateaued. In contrast, disease-modifying factors have not changed over time in western China. Further studies are needed to explore what may contribute to these findings.
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http://dx.doi.org/10.1016/j.jns.2019.06.026DOI Listing
August 2019

The use of of inulin, maltitol and lecithin as fat replacers and plasticizers in a model reduced-fat mozzarella cheese-like product.

J Sci Food Agric 2019 Sep 30;99(12):5586-5593. Epub 2019 Jun 30.

Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin, China.

Background: Mono-, di- and oligosaccharides, polyhydric alcohols and lipids are three main types of plasticizers used to process food materials. In the present study, inulin, maltitol and lecithin were selected as representative oligosaccharide, polyhydric alcohol and lipid fat replacers, respectively. Their effects on the physicochemical properties of reduced-fat mozzarella cheese were evaluated.

Results: Lecithin reduced the hardness and increased the degree of free oil released. Inulin and lecithin decreased the hydrophobic interaction of reduced-fat cheese. Maltitol improved the elasticity of the reduced-fat cheese and increased the hydrophobic interaction within the casein matrix. Maltitol-added cheese had a lower glass transition temperature (T ) than the other cheeses. Maltitol significantly improved the stretchability of the reduced-fat cheese.

Conclusion: The results obtained in the present study suggest that maltitol is an effective fat replacer in reduced-fat mozzarella cheese and might enhance the cheese's functional properties. The T of cheese was related to the water and fat content, fat replacer addition and cross-linking degree of casein. The relationship between T and the physicochemical properties of cheese will be studied in further research. © 2019 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.9835DOI Listing
September 2019

Microplastics and nanoplastics: would they affect global biodiversity change?

Environ Sci Pollut Res Int 2019 Jul 17;26(19):19997-20002. Epub 2019 May 17.

College of Environmental Science and Engineering, Hunan University and Key Laboratory of Environmental Biology and Pollution Control (Hunan University), Ministry of Education, Changsha, 410082, People's Republic of China.

Micro(nano)plastics, new emerging contaminants, are ubiquitously found in the environment due to continuous release and accumulation. Widespread micro(nano)plastics can increase their exposure to organisms, pose threats to the ecological environment and human health, and potentially result in global biodiversity changes. Research has been started on micro(nano)plastics regarding their environmental distribution, contamination sources, and methods and technologies for analysis, as well as the environmental impacts and ecological effects on organisms ingesting micro(nano)plastics. However, limited information focused on the consequences of global biodiversity has been reported and the research approaches on biodiversity change caused by micro(nano)plastics are still seldom developed. Recently, researchers in environmental and ecological groups have begun to be conscious of the relationship between micro(nano)plastics and biodiversity. Even so, more efforts are needed to assess the impacts of micro(nano)plastics on this subject, as well as the interactions between organisms and micro(nano)plastics.
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http://dx.doi.org/10.1007/s11356-019-05414-5DOI Listing
July 2019

Multifunctional Magnetic Nanoplatform Eliminates Cancer Stem Cells via Inhibiting the Secretion of Extracellular Heat Shock Protein 90.

Adv Healthc Mater 2019 07 10;8(13):e1900160. Epub 2019 Apr 10.

Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei University, Baoding, 071002, P. R. China.

Cancer stem cells (CSCs) are responsible for malignant tumor initiation, recurrences, and metastasis. Therefore, targeting CSCs is a promising strategy for the development of cancer therapies. A big challenge for CSC-based cancer therapy is the overexpression of therapeutic stress protein, heat shock protein 90 (Hsp90), which protects CSCs from further therapeutic-induced damage, leading to the failure of treatment. Thus, efficient strategies to target CSCs are urgently needed for cancer therapy. To this end, a multifunctional nanoparticle (MNP) for CSC-based combined thermotherapy and chemotherapy is reported. This strategy dramatically suppresses tumor growth in breast CSC xenograft-bearing mice. Furthermore, a new mechanism is present that the MNP exerts its striking effects on CSCs by inhibiting the secretion of extracellular Hsp90 (eHsp90), resulting in the interruption of several key signaling pathways. These findings open new perspectives on the use of an MNP for effective CSC-based cancer treatment by inhibiting the function of eHsp90.
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http://dx.doi.org/10.1002/adhm.201900160DOI Listing
July 2019